SB L3 - Neurogenisis

Question 1

What is adult neurongenisis

Answer 1

the ability of the adult brain to generate new neurones

proliferation, migration, differentiation, survival, intergration - into a funcitoning network

Question 2

Does adult neurogenesis take place all over the brain?

Answer 2

no - localized to discrete brain regions

e.g. hippocampus

Question 3

Define stem cells
Progenitor cells
Precursos cells

Answer 3

Stem cells – able to proliferate, to self-renew and to differentiate to multiple lineages
Progenitor cells – proliferate, differentiate but do not self-renew
Precursor cells – both stem cells and progenitor cells

Question 4

major relay station for information from the cortex to other regions is…..

Answer 4

Hippocampus - key place for neurogenisis

Lateral ventricles are a site where neurogenesis occurs,. Subventricular zone gives rise to cells that migrate to the hippocampus.

Question 5

What are the key cells for neurogenesis, where are they found?

Answer 5

Granule cells in the dendate gyrus.

Theses are replaced with the new neurons from neurogenesis.

Question 6

Hip is associates with …………… and ………….

also connected ro ……………… and ………………. associated with what funcitons?

Answer 6

Hippocampus is related to learning and memory but also anxiety because it has reciprocal connections with

• prefrontal cortex (mood)
• amygdala (emotion and fear).

Question 7

What does BrdU stand for?

What is it?

Answer 7

Bromodeoyuridine

-

Question 8

What does BrdU stand for?

What is it?

Answer 8

Bromodeoyuridine
- a uridine derivative that can be incorporated specifically into DNA in place of thyamine

(it’s not something endogenous so we know where it comes from)

Question 9

What do we do with the BrdU?

Answer 9

You can take the brain slice and use antibodies to see the cells

Question 10

What does BrdU show?

What else should you look for?

Answer 10

numbers of cells proliferating and dividing (but no whether they are neurones/ will they be intergrated into a funcitoning network?)

Look for markers of neuronal cells (they express different markers at different stages of development)

Question 11

What did ……….REF ….find about adult neurogenisis from 14C?

Answer 11

Spalding et al. 2013:

• used concentration of nuclear bomb-test-derived 14C in genomic DNA to look at generation of hippocampal cells in humans
• one third of hippocamal neurones is subject to exchange

-700 new neurons are added per day, (annual turnover of 1.75% of the neurons within the renewing fraction), with a modest decline during aging.
(this is much higher than rodents)

Question 12

5 factors that reglate neurogenisis

we won’t focus in these but good examples

Answer 12

1. Intrinsic cell programming
   
   • Transcription factors involved in initiation of proliferation
2. Neurotransmitters
   - 5-HT, NA, DA
3. Neurotrophic factors
   - BDNF, NGF, VEGF
4. Corticosteroids
5. Environmental stimuli

Question 13

5 factors that reglate neurogenisis

we won’t focus in these but good examples

Answer 13

1. Intrinsic cell programming
   
   • Transcription factors involved in initiation of proliferation
2. Neurotransmitters
   - 5-HT, NA, DA
3. Neurotrophic factors
   - BDNF, NGF, VEGF
4. Corticosteroids
5. Environmental stimuli

Question 14

Where can we find 5HT neurones in the DG?

What is the effect of activation/blockage?

What is the effect of lesioning?

Answer 14

subgranular layer

Activation/blockade of multiple 5-HT receptors alters proliferation

Lesioning 5-HT neurons reduces the proliferation of hippocampal cells

Question 15

effect of NA on nerogenesis?

Answer 15

NA depletion significantly decreases proliferation (but not survival) in SGL

Question 16

effect of DA on neurogenesis?

Answer 16

DA reported to have both +/- role in regulating proliferation in SVZ

Question 17

effect of ACh on neurogenisis?

Answer 17

Lesioning forebrain ACh neurons reduces, and blockade of ChE increases, proliferation

Question 18

What can we see by comparing the locolization of neurotransmitters?

Answer 18

Perhaps neurotransmitters define the localization where neurogenesis occurs.

Question 19

What are neurotrophins?

Answer 19

Provide trophic or neurtriant support to neurones and act as a growth factor

thought to stimulate neurogenisis.

Question 20

Neurotrophic growth factor family has …. proteins (including …………)

Answer 20

4 proteins
(including brain derived neurotrophic factor)

These proteins have structural similarity. All produced from a pre-protein chopped to make a mature protein.

Question 21

Where do neurptrophic factors bind?

Answer 21

to tropomyosin receptor kinases TrkA, B and C

Question 22

BDNF binds to

Answer 22

Trk B receptor.

Question 23

When neurotrophic growth factors bind what pathways are activated (3)

Answer 23

• Protein kinases B factor crucial for survival
• PLC gamma for activity dpendent plasticity
• ERK differentiation and survival

Question 24

What is the endogenous GC in rats?

Answer 24

cortisone

Question 25

What happens to neurogen when rat is treated with cortisone actuely

Answer 25

significant decrease in the density of [3H]thymidine-labeled cells in the hilus of the dentate gyrus.

Question 26

What happens when you give a rat an adrenalectomy?

Answer 26

significant increase in the number of neuron specific enolase-immunoreactive [3H]thymidine labeled cells in the granule cell layer compared to sham operation.

Question 27

Corticosteroids increase or decrease neurogenisis?

Answer 27

decrease

Can progenitor cells respond to corticosteroids? Or is it survival of neurones that is affected?